Adolescents with substance use disorders frequently suffer from concomitant psychiatric disorders. Unfortunately, substance use problems among adolescents presenting for psychiatric treatment are often not adequately assessed or addressed despite the deleterious consequences of this comorbid psychopathology. The overall objective of this research program is to develop effective brief intervention approaches to address substance use problems in high-risk adolescents with comorbid psychiatric disorders, and to advance our knowledge of the relationship between psychiatric and substance use disorders within the context of a treatment outcome study. The proposed study will test the comparative efficacy of a tailored, social learning-based brief motivational intervention with personalized feedback compared to treatment as usual for reducing substance use in adolescents hospitalized with comorbid substance use and psychiatric disorders. We will also test the effects of treatment on intermediate variables such as substance use problems, psychiatric symptoms, motivation to change and post-hospitalization treatment involvement, and will examine the mechanisms of change. The study is a randomized (by cohort), two group design with repeated measures over time, comparing the efficacy of: (a) a tailored, brief motivational interviewing intervention with personalized feedback (MI) vs. (b) treatment as usual (TAU). A sample of 250 adolescent psychiatric inpatients between the ages of 13 and 17 will be recruited into the study. Subjects will meet criteria for one of more DSM-IV (non-nicotine) substance use disorders and for one or more additional current Axis I disorders, other than a substance use disorder. Subjects will be followed for 12 months, and self-reported abstinence from substance use will be verified using breath analysis and saliva drug tests. We expect that this study will result in the development of a specialized, efficacious intervention approach for the significant percentage of adolescents with comorbid substance use and psychiatric disorders, and will therefore have important clinical and public health implications.